气候变化领域集成服务门户(CCPortal): CRY2 missense mutations suppress P53 and enhance cell growth

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DOI	10.1073/pnas.2101416118
	CRY2 missense mutations suppress P53 and enhance cell growth
	Chan A.B.; Parico G.C.G.; Fribourgh J.L.; Ibrahim L.H.; Bollong M.J.; Partch C.L.; Lamia K.A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:27
英文摘要	Disruption of circadian rhythms increases the risk of several types of cancer. Mammalian cryptochromes (CRY1 and CRY2) are circadian transcriptional repressors that are related to DNA-repair enzymes. While CRYs lack DNA-repair activity, they modulate the transcriptional response to DNA damage, and CRY2 can promote SKP1 cullin 1–F-box (SCF)FBXL3-mediated ubiquitination of c-MYC and other targets. Here, we characterize five mutations in CRY2 observed in human cancers in The Cancer Genome Atlas. We demonstrate that two orthologous mutations of mouse CRY2 (D325H and S510L) accelerate the growth of primary mouse fibroblasts expressing high levels of c-MYC. Neither mutant affects steady-state levels of overexpressed c-MYC, and they have divergent impacts on circadian rhythms and on the ability of CRY2 to interact with SCFFBXL3. Unexpectedly, stable expression of either CRY2 D325H or of CRY2 S510L robustly suppresses P53 target-gene expression, suggesting that this may be a primary mechanism by which they influence cell growth. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Circadian clocks; Cryptochromes; Tumor suppressor protein P53
语种	英语
scopus关键词	Cry2 protein, mouse; cryptochrome; F box protein; protein p53; transcription factor ARNTL; transcription factor CLOCK; animal; cell proliferation; gene expression regulation; genetic transcription; genetics; human; metabolism; missense mutation; mouse; protein analysis; Animals; ARNTL Transcription Factors; Cell Proliferation; CLOCK Proteins; Cryptochromes; F-Box Proteins; Gene Expression Regulation, Neoplastic; Humans; Mice; Mutation, Missense; Protein Interaction Maps; Transcription, Genetic; Tumor Suppressor Protein p53
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251142
作者单位	Department of Molecular Medicine, The Scripps Research Institute, San Diego, CA 92037, United States; Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, United States; Department of Chemistry, The Scripps Research Institute, San Diego, CA 92037, United States
推荐引用方式 GB/T 7714	Chan A.B.,Parico G.C.G.,Fribourgh J.L.,et al. CRY2 missense mutations suppress P53 and enhance cell growth[J],2021,118(27).
APA	Chan A.B..,Parico G.C.G..,Fribourgh J.L..,Ibrahim L.H..,Bollong M.J..,...&Lamia K.A..(2021).CRY2 missense mutations suppress P53 and enhance cell growth.Proceedings of the National Academy of Sciences of the United States of America,118(27).
MLA	Chan A.B.,et al."CRY2 missense mutations suppress P53 and enhance cell growth".Proceedings of the National Academy of Sciences of the United States of America 118.27(2021).